| Objective:By injecting TWEAK into the ventricles of stroke rats,the behavioral changes,changes of inflammatory factors in brain tissue,apoptosis and permeability of blood-brain barrier of hippocampus and prefrontal cortex were observed,the relationship between TWEAK and post-stroke depression(PSD)was explored.Methods:A two-step method was used to make a PSD model.First,an ischemia model was established,and then TWEAK was injected into the lateral ventricle.The rats were randomly divided into a sham operation group(Control group),a stroke group(MCAO group),a homotype control group(MCAO + DMSO group),and a PSD group(MCAO + TWEAK group).The behavioral changes of rats were studied by weight,open field test,forced swimming test,and sucrose preference test;RT-PCR was used to detect the expression of inflammatory cytokines IL-1 ?,IL-6 and TNF-? mRNAs in hippocampus;TUNEL staining marked apoptosis in PFC tissues;The expression of AQP-4 were detected by immunohistochemistry.Results:(1)Behavioral test:(1)body weight: Within 14 days after MCAO,there was no significant difference in body weight among the groups.From the 14 th day after operation,the body weight of the PSD group gradually decreased,while that of the other groups showed an upward trend.On the 32 nd day,the weight loss in the PSD group was the most significant,and there were significant differences compared with the sham operation group,the stroke group and the same type control group(P < 0.05).The body weight of PSD group began to show statistical significance from the 22 nd day,and the weight loss on the 32 nd day was the most obvious compared with that on the 14 th and 22 nd day.(2)sucrose preference test: Among the groups after the experiment,the sugar water preference rate in the PSD group was the lowest,which was statistically significant compared with the sham operation group and the same type control group(P < 0.05).(3)open field test: In the course of the experiment,the immobility time of each group increased gradually.From the 14 th day(from the beginning of intracerebroventricular injection),the immobility time of each group gradually prolonged,and the difference was the most significant on the 32 nd day.There was significant difference between PSD group and sham operation group,homotype control group and stroke group(P < 0.05).In PSD group,the immobility time began to show statistical significance on the 22 nd day(P < 0.05).The immobility time on the 32 nd day of the PSD group,was significantly longer than that on the 14 th and 22 nd days(P < 0.05).(4)forced swimming test: Although the immobility time in the PSD group was longer than that in the sham operation group,the stroke group and the same type control group,there was no statistical significance(P > 0.05).(2)TUNEL staining results: In the prefrontal cortex of rats,TUNEL positive cells were scattered and light in color in the sham operated group,while those in the PSD group were dense and dark in color;the number of positive cells in the prefrontal cortex of rats in the PSD group,the same type control group and the stroke group was significantly higher than that in the sham operated group(P < 0.05);the number of positive cells in the PSD group was higher than that in the sham operated group,the same type control group and the stroke group(P < 0.05)It was improved(P < 0.05).In CA1 area of hippocampus of rats,the distribution of TUNEL positive cells in sham operation group was sparse,and the color of TUNEL positive cells in PSD group was lighter than that in other three groups(P < 0.05).(3)RT-PCR: The levels of IL-1 ?,IL-6 and TNF-? mRNA in hippocampus of PSD group were significantly higher than those of sham operation group,homotype control group and stroke group.(P < 0 05).(4)Immunohistochemical results: the number of AQP-4 protein positive cells in prefrontal cortex of PSD group was significantly higher than that of sham operation group,control group and stroke group(P < 0.05).Hippocampal CA1 area: compared with the sham operation group,the number of AQP-4 protein positive cells in the stroke group,the same type control group and the PSD group increased in turn,and the number of positive cells in the PSD group increased significantly compared with the stroke group and the control group(P < 0.05).Conclusion:(1)Intracerebroventricular injection of TWEAK can induce depression-like behavior after stroke,which provides a new method to study the inflammatory mechanism of poststroke depression.(2)Intraventricular injection of TWEAK can induce apoptosis of prefrontal cortex and hippocampal CA1 area,change of BBB,and increase of expression of central system proinflammatory factors,suggesting that TWEAK / Fn14 signaling pathway may be a potential therapeutic target for post-stroke depression. |
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